Optical analysis system for dynamic, real-time detection and measurement

ABSTRACT

A system and a method for real-time processing and monitoring, the system including a light source to provide an illumination light and a calibration light are provided. The system includes an optical element to separate the illumination light and the calibration light; an optical element to direct the illumination light to a sample; an optical element to direct the calibration light to a first detector and a second detector; an optical element to collect light backscattered from the sample; an optical element to separate light backscattered from the sample into a first scattered light portion and a second scattered light portion; an optical element to direct the first scattered light portion through at least one multivariate optical element to the first detector; and an optical element to direct the second scattered light portion to the second detector.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 12/094,465, entitled “OPTICAL ANALYSIS SYSTEM FOR DYNAMIC,REAL-TIME DETECTION AND MEASUREMENT,” incorporated herein by referencein its entirety, for all purposes, and which is a U.S. National Stage ofPCT application no. PCT/US06/08972, filed on Mar. 10, 2006, incorporatedherein by reference in its entirety, and which claims priority of U.S.provisional patent application No. 60/740,054 filed on Nov. 28, 2005 andNo. 60/773,276 filed on Feb. 14, 2006, both incorporated herein byreference in their entirety, for all purposes.

FIELD OF THE INVENTION

The present invention relates to improvements related to system design,fabrication and operation of multivariate optical elements. Moreparticularly, the invention relates to methodologies of usingmultivariate optical computing systems to illuminate a sample in whichinformation about the sample can be analyzed from the reflected ortransmitted light in real time or near real time.

BACKGROUND OF THE INVENTION

Light conveys information through data. When light interacts withmatter, for example, it carries away information about the physical andchemical properties of the matter. A property of the light, for example,its intensity, may be measured and interpreted to provide informationabout the matter with which it interacted. That is, the data carried bythe light through its intensity may be measured to derive informationabout the matter. Similarly, in optical communications systems, lightdata is manipulated to convey information over an optical transmissionmedium, for example fiber optic cable. The data is measured when thelight signal is received to derive information.

In general, a simple measurement of light intensity is difficult toconvert to information because it likely contains interfering data. Thatis, several factors may contribute to the intensity of light, even in arelatively restricted wavelength range. It is often impossible toadequately measure the data relating to one of these factors since thecontribution of the other factors is unknown.

It is possible, however, to derive information from light. An estimatemay be obtained, for example, by separating light from several samplesinto wavelength bands and performing a multiple linear regression of theintensity of these bands against the results of conventionalmeasurements of the desired information for each sample. For example, apolymer sample may be illuminated so that light from the polymer carriesinformation such as the sample's ethylene content. Light from each ofseveral samples may be directed to a series of bandpass filters whichseparate predetermined wavelength bands from the light. Light detectorsfollowing the bandpass filters measure the intensity of each light band.If the ethylene content of each polymer sample is measured usingconventional means, a multiple linear regression of ten measuredbandpass intensities against the measured ethylene content for eachsample may produce an equation such as:y=a ₀ +a ₁ w ₁ +a ₂ w ₂ + . . . +a ₁₀ w ₁₀  (“Equation 1”)where y is ethylene content, a, are constants determined by theregression analysis, and w, is light intensity for each wavelength band.

Equation 1 may be used to estimate ethylene content of subsequentsamples of the same polymer type. Depending on the circumstances,however, the estimate may be unacceptably inaccurate since factors otherthan ethylene may affect the intensity of the wavelength bands. Theseother factors may not change from one sample to the next in a mannerconsistent with ethylene.

A more accurate estimate may be obtained by compressing the data carriedby the light into principal components. To obtain the principalcomponents, spectroscopic data is collected for a variety of samples ofthe same type of light, for example from illuminated samples of the sametype of polymer. For example, the light samples may be spread into theirwavelength spectra by a spectrograph so that the magnitude of each lightsample at each wavelength may be measured. This data is then pooled andsubjected to a linear-algebraic process known as singular valuedecomposition (SVD). SVD is at the heart of principal componentanalysis, which should be well understood in this art. Briefly,principal component analysis is a dimension reduction technique, whichtakes m spectra with n independent variables and constructs a new set ofeigenvectors that are linear combinations of the original variables. Theeigenvectors may be considered a new set of plotting axes. The primaryaxis, termed the first principal component, is the vector, whichdescribes most of the data variability. Subsequent principal componentsdescribe successively less sample variability, until only noise isdescribed by the higher order principal components.

Typically, the principal components are determined as normalizedvectors. Thus, each component of a light sample may be expressed as x,z, where x, is a scalar multiplier and z, is the normalized componentvector for the nth component. That is, z, is a vector in amulti-dimensional space where each wavelength is a dimension. As shouldbe well understood, normalization determines values for a component ateach wavelength so that the component maintains it shape and so that thelength of the principal component vector is equal to one. Thus, eachnormalized component vector has a shape and a magnitude so that thecomponents may be used as the basic building blocks of all light sampleshaving those principal components. Accordingly, each light sample may bedescribed in the following format by the combination of the normalizedprincipal components multiplied by the appropriate scalar multipliers:x ₁ z ₁ +x ₂ z ₂ + . . . x _(n) z _(n).

The scalar multipliers x, may be considered the “magnitudes” of theprincipal components in a given light sample when the principalcomponents are understood to have a standardized magnitude as providedby normalization.

Because the principal components are orthogonal, they may be used in arelatively straightforward mathematical procedure to decompose a lightsample into the component magnitudes, which accurately describe the datain the original sample. Since the original light sample may also beconsidered a vector in the multi-dimensional wavelength space, the dotproduct of the original signal vector with a principal component vectoris the magnitude of the original signal in the direction of thenormalized component vector. That is, it is the magnitude of thenormalized principal component present in the original signal. This isanalogous to breaking a vector in a three dimensional Cartesian spaceinto its X, Y and Z components. The dot product of the three-dimensionalvector with each axis vector, assuming each axis vector has a magnitudeof 1, gives the magnitude of the three dimensional vector in each of thethree directions. The dot product of the original signal and some othervector that is not perpendicular to the other three dimensions providesredundant data, since this magnitude is already contributed by two ormore of the orthogonal axes.

Because the principal components are orthogonal, or perpendicular, toeach other, the dot, or direct, product of any principal component withany other principal component is zero. Physically, this means that thecomponents do not interfere with each other. If data is altered tochange the magnitude of one component in the original light signal, theother components remain unchanged. In the analogous Cartesian example,reduction of the X component of the three dimensional vector does notaffect the magnitudes of the Y and Z components.

Principal component analysis provides the fewest orthogonal componentsthat can accurately describe the data carried by the light samples.Thus, in a mathematical sense, the principal components are componentsof the original light that do not interfere with each other and thatrepresent the most compact description of the entire data carried by thelight. Physically, each principal component is a light signal that formsa part of the original light signal. Each has a shape over somewavelength range within the original wavelength range. Summing theprincipal components produces the original signal, provided eachcomponent has the proper magnitude.

The principal components comprise a compression of the data carried bythe total light signal. In a physical sense, the shape and wavelengthrange of the principal components describe what data is in the totallight signal while the magnitude of each component describes how much ofthat data is there. If several light samples contain the same types ofdata, but in differing amounts, then a single set of principalcomponents may be used to exactly describe (except for noise) each lightsample by applying appropriate magnitudes to the components.

The principal components may be used to accurately estimate informationcarried by the light. For example, suppose samples of a certain brand ofgasoline, when illuminated, produce light having the same principalcomponents. Spreading each light sample with a spectrograph may producewavelength spectra having shapes that vary from one gasoline sample toanother. The differences may be due to any of several factors, forexample differences in octane rating or lead content.

The differences in the sample spectra may be described as differences inthe magnitudes of the principal components. For example, the gasolinesamples might have four principal components. The magnitudes x, of thesecomponents in one sample might be J, K, L, and M, whereas in the nextsample the magnitudes may be 0.94 J, 1.07K, 1.13 L and 0.86M. As notedabove, once the principal components are determined, these magnitudesexactly describe their respective light samples.

Refineries desiring to periodically measure octane rating in theirproduct may derive the octane information from the component magnitudes.Octane rating may be dependent upon data in more than one of thecomponents. Octane rating may also be determined through conventionalchemical analysis. Thus, if the component magnitudes and octane ratingfor each of several gasoline samples are measured, a multiple linearregression analysis may be performed for the component magnitudesagainst octane rating to provide an equation such as:y=a ₀ +a ₁ x ₁ +a ₂ x ₂ +a ₃ x ₃ +a ₄ x ₄  (“Equation 2”)

where y is octane rating, a_(n), are constants determined by theregression analysis, and x₁, x₂, x₃ and x₄ are the first, second, thirdand fourth principal component magnitudes, respectively.

Using Equation 2, which may be referred to as a regression vector,refineries may accurately estimate octane rating of subsequent gasolinesamples. Conventional systems perform regression vector calculations bycomputer, based on spectrograph measurements of the light sample bywavelength. The spectrograph system spreads the light sample into itsspectrum and measures the intensity of the light at each wavelength overthe spectrum wavelength range. If the regression vector in the Equation2 form is used, the computer reads the intensity data and decomposes thelight sample into the principal component magnitudes x, by determiningthe dot product of the total signal with each component. The componentmagnitudes are then applied to the regression equation to determineoctane rating.

To simplify the procedure, however, the regression vector is typicallyconverted to a form that is a function of wavelength so that only onedot product is performed. Each normalized principal component vector z,has a value over all or part of the total wavelength range. If eachwavelength value of each component vector is multiplied by theregression constant a, corresponding to the component vector, and if theresulting weighted principal components are summed by wavelength, theregression vector takes the following form:y=a ₀ +b ₁ u ₁ +b ₂ u ₂ + . . . +b _(n) u _(n)  (“Equation 3”)

where y is octane rating, a₀ is the first regression constant fromEquation 2, b, is the sum of the multiple of each regression constant anfrom Equation 2 and the value of its respective normalized regressionvector at wavelength n, and u, is the intensity of the light sample atwavelength n. Thus, the new constants define a vector in wavelengthspace that directly describes octane rating. The regression vector in aform as in Equation 3 represents the dot product of a light sample withthis vector.

Normalization of the principal components provides the components withan arbitrary value for use during the regression analysis. Accordingly,it is very unlikely that the dot product result produced by theregression vector will be equal to the actual octane rating. The numberwill, however, be proportional to the octane rating. The proportionalityfactor may be determined by measuring octane rating of one or moresamples by conventional means and comparing the result to the numberproduced by the regression vector. Thereafter, the computer can simplyscale the dot product of the regression vector and spectrum to produce anumber approximately equal to the octane rating.

In a conventional spectroscopy analysis system, a laser directs light toa sample by a bandpass filter, a beam splitter, a lens and a fiber opticcable. Light is reflected back through the cable and the beam splitterto another lens to a spectrograph. The spectrograph separates light fromthe illuminated sample by wavelength so that a detection device such asa charge couple detector can measure the intensity of the light at eachwavelength. The charge couple detector is controlled by controller andcooled by a cooler. The detection device measures the light intensity oflight from the spectrograph at each wavelength and outputs this datadigitally to a computer, which stores the light intensity over thewavelength range. The computer also stores a previously derivedregression vector for the desired sample property, for example octane,and sums the multiple of the light intensity and the regression vectorintensity at each wavelength over the sampled wavelength range, therebyobtaining the dot product of the light from the substance and theregression vector. Since this number is proportional to octane rating,the octane rating of the sample is identified.

Since the spectrograph separates the sample light into its wavelengths,a detector is needed that can detect and distinguish the relativelysmall amounts of light at each wavelength. Charge couple devices providehigh sensitivity throughout the visible spectral region and into thenear infrared with extremely low noise. These devices also provide highquantum efficiency, long lifetime, imaging capability and solid-statecharacteristics. Unfortunately, however, charge couple devices and theirrequired operational instrumentation are very expensive. Furthermore,the devices are sensitive to environmental conditions. In a refinery,for example, they must be protected from explosion, vibration andtemperature fluctuations and are often placed in protective housingsapproximately the size of a refrigerator. The power requirements,cooling requirements, cost, complexity and maintenance requirements ofthese systems have made them impractical in many applications.

Multivariate optical computing (MOC) is a powerful predictivespectroscopic technique that incorporates a multi-wavelength spectralweighting directly into analytical instrumentation. This is in contrastto traditional data collection routines where digitized spectral data ispost processed with a computer to correlate spectral signal with analyteconcentration. Previous work has focused on performing such spectralweightings by employing interference filters called Multivariate OpticalElements (MOEs). Other researchers have realized comparable results bycontrolling the staring or integration time for each wavelength duringthe data collection process. All-optical computing methods have beenshown to produce similar multivariate calibration models, but themeasurement precision via an optical computation is superior to atraditional digital regression.

MOC has been demonstrated to simplify the instrumentation and dataanalysis requirements of a traditional multivariate calibration.Specifically, the MOE utilizes a thin film interference filter to sensethe magnitude of a spectral pattern. A no-moving parts spectrometerhighly selective to a particular analyte may be constructed by designingsimple calculations based on the filter transmission and reflectionspectra. Other research groups have also performed optical computationsthrough the use of weighted integration intervals and acousto-opticaltunable filters digital mirror arrays and holographic gratings.

The measurement precision of digital regression has been compared tovarious optical computing techniques including MOEs, positive/negativeinterference filters and weighted-integration scanning opticalcomputing. In a high signal condition where the noise of the instrumentis limited by photon counting, optical computing offers a highermeasurement precision when compared to its digital regressioncounterpart. The enhancement in measurement precision for scanninginstruments is related to the fi-action of the total experiment timespent on the most important wavelengths. While the detector integratesor co-adds measurements at these important wavelengths, the signalincreases linearly while the noise increases as a square root of thesignal. Another contribution to this measurement precision enhancementis a combination of the Felgott's and Jacquinot's advantage, which ispossessed by MOE optical computing.

While various methodologies have been developed to enhance measurementaccuracy in Optical Analysis Systems, the industry requires a system inwhich the spectral range of the illumination source can be controlled;in which light can be shined directly onto a sample with or withoutfiber optic probes; and in which the reflected or transmitted light canbe analyzed in real time or near real time.

SUMMARY OF THE INVENTION

According to some embodiments a system for real-time processing andmonitoring may include a light source to provide an illumination lightand a calibration light; an optical element to separate the illuminationlight and the calibration light; an optical element to direct theillumination light to a sample; an optical element to direct thecalibration light to a first detector and a second detector; an opticalelement to collect light backscattered from the sample; an opticalelement to separate light backscattered from the sample into a firstscattered light portion and a second scattered light portion; an opticalelement to direct the first scattered light portion through at least onemultivariate optical element to the first detector; and an opticalelement to direct the second scattered light portion to the seconddetector.

According to some embodiments a method for real-time processing andmonitoring may include separating a source light into an illuminationlight and a calibration light; illuminating a sample with theillumination light; dividing light carrying information about the samplewith a beam splitter into a first light portion and a second lightportion; after dividing the light with the beam splitter, directing thefirst light portion through at least one multivariate optical element toproduce a first signal; detecting the first signal at a first detector;directing the second light portion in a direction of a second detector,the second detector configured to detect the second light portion;detecting a portion of the calibration light at the first detector; anddetermining at least one selected property of the sample based upon afirst detector output and a second detector output.

In some embodiments a method for real-time processing and monitoringincludes positioning a sample proximal to an optic window in an opticalsensor; separating a source light into a spectral-specific light and acalibration light; illuminating a powder with the spectral-specificlight through an optic window, the optic window configured to focus thespectral-specific light into the sample; dividing light carryinginformation about the powder with a beam splitter into a first lightportion and a second light portion, the first light portion and thesecond light portion having substantially similar spectralcharacteristics; directing the first light portion through at least onemultivariate optical element to produce a first signal; detecting thefirst signal at a first detector; detecting a portion of the calibrationlight at the first detector; directing the second light portion in adirection of a second detector, the second detector configured to detectthe second light portion; and determining at least one selected propertyof the sample based upon a first detector output and a second detectoroutput.

Other aspects and advantages of the invention are described in greaterdetail below.

BRIEF DESCRIPTION OF THE DRAWINGS

A full and enabling disclosure of the present invention, including thebest mode thereof to one skilled in the art, is set forth moreparticularly in the remainder of the specification, including referenceto the accompanying figures, in which:

FIG. 1 is a top perspective view of one embodiment of a real timemeasurement system according to an aspect of the present invention;

FIG. 2 is a schematic view of a concentric cavity as in FIG. 1 inaccordance with a further aspect of the present invention;

FIG. 3 is schematic plan view of another embodiment of a real timemeasurement system according to another aspect of the present invention;

FIG. 4A is a perspective view of a retro-reflecting mirror for use inthe embodiments of FIGS. 1-3 according to a further aspect of theinvention;

FIG. 4B is an end view of the retro-reflecting mirror as in FIG. 4A;

FIG. 5 is a schematic view of an implementation in which material(s)undergoing a process step may be measured in real-time using the presentinvention;

FIG. 6 is another schematic view of a real-time process measurementusing the present invention; and

FIG. 7 is a schematic view of using the present invention at multipleprocess stages to monitor material characteristics.

DETAILED DESCRIPTION OF THE DISCLOSURE

Detailed reference will now be made to the drawings in which examplesembodying the present invention are shown. The detailed description usesnumerical and letter designations to refer to features of the drawings.Like or similar designations of the drawings and description have beenused to refer to like or similar parts of the invention. The drawingsand detailed description provide a full and written description of theinvention, and of the manner and process of making and using it, so asto enable one skilled in the pertinent art to make and use it, as wellas the best mode of carrying out the invention.

However, the examples set forth in the drawings and detailed descriptionare provided by way of explanation only and are not meant as limitationsof the invention. The present invention thus includes any modificationsand variations of the following examples as come within the scope of theappended claims and their equivalents.

As generally shown in FIGS. 1 and 2, an optical analysis systemaccording to an aspect of the invention is designated by the elementnumber 10. The system 10 is designed around at least one applicationspecific multivariate optical element (MOE) based on spectra typicallyprovided by an end-user. System design takes into account representativespectra of compounds of interest, basic and expected concentrations ofinterest across a range of expected interferents. Also, the system 10incorporates the desired spectral regions (UV, VIS, NIR, MIR,

IR) of interest. In the embodiment shown in FIG. 1, the optical analysissystem 10 broadly includes a housing 12, a plurality of illumination orlight sources 14A, 14B, a concentric light tube or cavity 22, a focusinglens 26, at least one beam splitter 28, a first detector 30 including amultivariate optical element 48 and a second detector 32. Although FIG.1 shows a generally square- or rectangle-shaped, metallic housing 12 andtwo detectors 30, 32 arranged therein, the skilled artisan willinstantly appreciate that a variety of shapes, dimensions, componentplacements and material makeup of the components can be substituted forthe examples shown according to various requirements such as governmentregulations, customer specifications and the like.

As used herein, the term “light” is broadly used to mean any form ofradiation or radiative energy including, for instance, visible light orlight in the infrared region. “Light” is also referred to herein as alight signal, a light beam, a light ray and the like to mean any form ofradiative energy in the electromagnetic spectrum. Similarly, the term“transmission” can mean transmission of radiative energy onto a surfaceof a sample; penetration, however slight, into a sample such as aparticulate sample or opaque fluid sample; or passage through a samplesuch as a fluid sample.

Moreover, as discussed below with respect to another embodiment of theinvention, a work piece or sample W can be analyzed using a PCR-typemodel without the beamsplitter 28 in an off-line approach. As usedherein, the work piece or sample W can mean an analyte undergoinganalysis over a range of conditions. The sample can be a solid or afluid including but not limited to a powder, a pharmaceutical powdermixed with lactose and other excipient materials, a chemical, a polymer,a petroleum product, a solution, a dispersion, an emulsion andcombinations of these solids and fluids.

The skilled artisan will also understand that although the system can bea measurement system operating in reflectance mode, the system can alsobe configured to operate in a transmission mode in which light is shonethrough the sample W from an incident side of the sample W to a similardetection system 110 on another side of the sample W. Alternatively, oradditionally, a mirrored surface 210 can be placed within thetransmissive sample to reflect the light back into the detection system10. Therefore, the invention is not limited only to the examples shownin the figures.

With more particular reference to FIG. 1, the housing 12 (shownpartially in phantom for clarity) can be metal such as stainless steel,a plastic material such as high-density polyethylene (HDPE) or anydurable material for protecting the components of the optical analysissystem 10. As shown, sampling of the sample W is accomplished through awindow 13 in the enclosed optical analysis system 10. Accordingly, theenclosed optical analysis system 10 can be used in a dangerous (e.g.,explosive) environment. As will be described in detail below, the window13 is transmissive in a known manner in a spectral region of interest.

As briefly introduced above, the illumination sources 14A, 14B arechosen to provide a source light 34, which has a spectral rangedetermined by a spectral range of interest for the intended samplemeasurement. The illumination sources 14A, 14B are also chosen based onreliability, intensity, temperature generation, and other factors. Theillumination sources 14A, 14B are also redundant to m her enhancereliability. As shown in FIG. 1, the redundant illumination sources 14A,14B can be oriented at 90 degrees from each other with a “50-50” beamsplitter 36 located near their center point to provide a constant sourceof illumination.

FIG. 1 further shows a plurality of lenses 16A, 16B, respectivelyassociated with each of the illumination sources 14A, 14B. The lenses16A, 16B are used to collect the light signal 34 from the illuminationsources 14A, 14B and to focus the light signal 34 on a modulator orchopper wheel 18, described below. As shown, the lenses 16A, 1 dB arepositioned to capture as much of the light signal 34 as possible fromthe illumination sources 14A, 14B. Additionally, a chopper-focusing lens17 is used to focus as much of the light signal 34 as possible throughthe chopper wheel 18. The skilled artisan will instantly recognize thelenses 16A, 16B, 17 are selected for focal length, position, material ofconstruction and the like to enhance transmission (reduce loss) of thelight signal 34. For example, in the design of the optical path, if theillumination sources 14A, 14B is a lamp, slight magnification ordemagnification of the source is generally obtained at the sample W,depending on the ratios of the focal length, e.g., of the lens 16A tothat placed after the illumination source 14A to collimate it.Ultimately, the image of the illumination source 14A on the sample W isdirected toward the detectors 30, 32 as described below and again withsome slight magnification or demagnification, depending on the ratios ofthe focal length, e.g., of the lenses 16A to that of, e.g., a lens 50placed before the detector 30 to focus a reflected light 46 onto thedetector 30. Thus, it should be understood that there is a relationshipbetween the focal lengths of the lenses 16A, 16B that must be maintainedin order to make sure the ultimate image of the source-excited region ofthe sample W that is formed on the detectors 30,32 is suited to thephysical dimensions of the detectors 30,32.

The skilled artisan will further appreciate that the lenses 16A, 16Bshown for example in FIG. 1 are plastic, Fresnel lenses well suited foruse in an infrared (IR) region of about 1000 nanometers (nm) to about3000 nm. However, the skilled artisan will understand that the lenses16A, 16B are not limited to only plastic, Fresnel lenses and that othertypes of lenses and materials such as glass can be used for theselenses.

As further shown in FIG. 1, the chopper wheel 18 includes a plurality ofalternating windows 38 and a plurality of alternating spokes 40. Thealternating windows 38 and spokes 40 modulate the light signal 34 fromabout 50 Hertz (Hz) to about 5000 Hz to enable a plurality ofphotodetectors 52,56 in the optical system 10 to perform properly, aswill be further described below. As shown in this example, the chopperwheel 18 is a 10-window chopper wheel rotating at 40 Hz, which providesa chopped signal of 400 Hz. The number and arrangement of the windows 38and spokes 40 and thus, the chopper frequency, are chosen based onseveral variables, including a rate of motion of the sample material Wmoving past the sampling window 13; a performance characteristic of thephotodetectors 52,56 and amplification system; a predetermined samplingrate of the data collection and analysis system 10; physical propertiesof a chopper motor (not shown), control system (not shown), and thechopper wheel 18 (including material(s) of the windows 38).

More particularly, the number of windows 38 in the chopper wheel 18 canbe adjusted to provide a suitable degree of signal modulation. In oneaspect of the invention, the chopper wheel 18 has open windows 38 andblack spokes 40, which block the light signal 34. In another aspect,different materials can be placed in the windows 38 to provide differentspectral characteristics for the various windows 38. Moreover, thetransmission characteristic of these windows 38 could be used as furtherspectral elements. The windows 38 can also contain multivariate opticalelements (MOE) such as those described below with respect to a MOE 48 ofthe MOE detector 30.

FIG. 1 also shows a plurality of bandpass filters or spectral elements20 located in a path of the light signal 34 after the light signal 34has passed through the chopper wheel 18. As briefly discussed above, thespectral elements 20 are selected based on a desired application; i.e.,to analyze a particular sample W. The spectral elements 20 are chosen sothat the spectral region of illumination covers the desired range; i.e.,related to a particular chemical material of interest. For example, if1500-2000 nanometers (nm) of light wavelengths is the desired spectralregion, the spectral elements 20 are selected to filter out wavelengthsare not in that region. An example of these spectral elements is aSCHOTT brand filter, which can be a long pass, short pass, or band passfilter. By way of further example but not of limitation, some suitablematerials for use as the spectral elements 20 are listed in thefollowing table.

TABLE 1 Properties of Select Transmitting Materials SWL LWL SolubilityHardness MP pH Material Comments cm−1 cm−1 RI g/100 g Kg/mm 2 ° C. RangeAMTIR SeAsGe glass 11000 593 2.5 0 170 370 1-9 BAF 2 Barium 66600 6911.45 0.17 82 1280 5-8 Flouride Ca F 2 Calcium 79500 896 1.4 0.0017 1581360 5-8 Flouride CsI Cesium 42000 172 1.73 44 20 621 NA Iodide, veryhygroscopic Diamond Type IIa, 30000 <2 2.4 0 5700 550 fp  1-14 strong IRabsorbance between 2700- 1800 cm−1 Ge Germanium, 5500 432 4 0 780 936 1-14 brittle, becomes opaque at elevated temperatures KBr Potassium48800 345 1.52 53 6 730 NA Bromide, most widely used for mid-IRapplications KCl Potassium 55600 385 1.45 35 7 776 NA Chloride KRS-5Thallium 17900 204 2.37 0.05 40 414 5-8 Bromide/ Thallium Iodide NaClSodium 52600 457 1.49 36 18 801 NA Chloride Polyethylene For Far-IR, 625<4 1.52 0 110 1.5-14  swells with some organic solvents SiO 2 Silicon50000 2315 1.53 0 460 1713  1-14 Dioxide Si Silicon, strong 8900 624.303.41 0 1150 1420  1-12 IR absorbance between 624- 590 cm−1 ZnS ZincSulfide 17000 690 2.2 0 240 1830 5-9 ZnSe Zinc Selenide 15000 461 2.4 0120 1526 5-9 Note: To convert from wavenumber (cm−1) to wavelength (μm),divide 10,000 by the wavenumber; e.g. 5500 cm−1 is equivalent to 1.8 μmor 1800 nm. SWL—Shortest wavelength for transmission, 1 mm, 50%transmission LWL—Longest wavelength for transmission, 1 mm, 50%transmission RI—Refractive Index, at relevant wavelength MP—Meltingpoint pH—negative log of hydrogen ion concentration

With reference now to FIGS. 1 and 2, the light signal 34 exits thespectral elements and reflects off a first mirror or turning mirror 24.It will be appreciated that although the turning mirror 24 is shown atan angle of about 45 degrees with the light signal 34 reflecting at theart, the turning mirror 24 can be a powered turning mirror powered by abattery, by electricity or the like. Further description of powersources and implementation with the turning mirror 24 is not necessaryfor one skilled in the art to understand this aspect of the invention.The skilled artisan will further appreciate that although the turningmirror 24 is shown as a unitary mirror, the invention can utilizemultiple mirrors arranged in or adjustable to a variety of positions.

As further shown in FIGS. 1 and 2, the filtered and reflected lightsignal 34 becomes a reflected light 44 after being reflected by theturning mirror 24. The reflected light 44 thus continues down theconcentric sampling tube 22, briefly introduced above, in a direction ofthe sample W. As shown and further described below, the concentric tube22 includes an inner annular region (also referred to as tube orchamber) 42A and an outer annular region 42B (also, tube or chamber). Inthis example, the reflected light 44 is reflected along the innerannular region 42A. It will be understood that the illumination sources14A, 14B and the detectors 30, 32 are shown in an exemplary orientationand can be reversed. It will be further appreciated that the lightsignal 34 and the reflected light 44 are shown collimated forsimplicity. However, the light signal 34 and the reflected light 44 maynot be completely collimated because the illumination sources 14A, 14Bcan be extended rather than point sources.

The focusing lens 26 in FIGS. 1 and 2 is located near an end of the tube22 proximate the sample W. As shown in this example, the end of the tube22 is sealed with the transmissive window 13. The transmissive window 13should be uniformly transmissive across wavelengths, but if it is not,the transmission characteristics of the transmissive window 13 are takeninto account for the design of the system 10 and in particular the MOE48. This embodiment may include an additional focusing lens 66, whichcan be solid or have one or more apertures as shown in FIG. 1. Theadditional focusing lens 66 is used to focus or collimate a carrierlight 46, described below, in a direction of the tube 22.

As further shown in FIGS. 1 and 2, the focusing lens 26 focuses thereflected light 44 onto, into or near the sample W via the transmissivewindow 13. In this example, the reflected light 44 is focused with afocal point 0-5 mm into the sample W. In addition to isolatingcomponents of the optical analysis system 10 from an externalenvironment, the transmissive window 13 further enables a mixing vesselor container C, which is being tested/sampled into, to remain intact. Asshown in this example, a one-inch (inner diameter) Swagelok brandconnector 62, available from Swagelok Corporation, Solon, Ohio, is usedto connect the optical analysis system 10 to the mixing vessel C. Thisarrangement permits the reflected light 44 to be sent down the tube 22(inner region 42A), interact with the material of interest W, reflectback up the tube 22 (outer region 42B), and be directed to the detectors30, 32 as further described below.

As most clearly shown in FIG. 2, a tube 58 defines an aperture 60 forpassage of the light signal 34 in a direction of the turning mirror 24.Separation of the illumination and reflection light paths or signals44,46 can be further defined or separated by physically separating theinner and outer regions 42A, 42B employing the tube 58. Any minimalreduction in light return of the carrier light 46 described below(caused by physical occupation of a portion of the outer region 42B bythe tube 58) is offset by improvement in the amount of backscatteredradiation returned to the detectors 30, 32 without encountering thesample W.

More specifically, the tube 58 is used to reduce a non-zero backgroundmeasurement. The non-zero background measurement can occur in an opticalsystem when a small amount of scattered light is returned to a detectoreven when no sample is present. Some of the scattered light can bereflected from a window, and some can come from the lenses themselves.

FIG. 2 shows that the tube 58 placed around the mirror 24 before thelens 26. The tube 58 reduces background signals by separating theexcitation and collection light paths 34,46 to minimize “cross-talk”. Asshown, the tube 58 defines an aperture 60 for passage of the lightsignal 34 in a direction of the turning mirror 24. As further shown, aconical extension 58A of the tube 58 can be placed after the mirror 24in a direction of the detector 30. A thickness of the tube 58 should beminimized.

Also shown in FIG. 2, the tube 58 can have specular interior andexterior surfaces as well as a highly reflective coating 58B, such asgold, applied by electrolysis deposition, evaporation or other thin filmcoating method. The coating 58B reflects rays 34,46 that wouldordinarily terminate at a surface of the tube 58 back into respectiveoptical paths from which they came. An image of the illumination source14A, 14B may be vignetted, but the “lost” light M the image is stillfocused to a spot within the zone illuminated by the illumination source14A, 14B. Likewise, the returning light outside the tube 58 can be keptfrom being lost by traveling inside an outer tube with a specularreflecting surface (not shown, but surrounding the outer light path).This will keep light loss to a minimum while keeping the input andoutput paths relatively isolated from one another.

As introduced above, the reflected light 46 shown in FIGS. 1 and 2travels back down the outer annular region 42A of the sampling tube 22,past the turning mirror 24. The light 46 reaches the beam splitter 28(one of its operating positions shown in phantom). The beam splitter 28divides the light 46 with a neutral or gray spectrum, sending some ofthe light 46 in a direction of the first or Multivariate Optical Element(MOE) detector 30 through the MOE 48, briefly introduced above, andthrough a first lens 50 onto the photo detector 52, also brieflyintroduced above. The beam splitter 28 sends some other portion of thelight 46 through a second lens 54 onto the other detector 56, alsobriefly introduced above.

As shown in the following table by example but not of limitation, somedetectors suitable for use as the detectors 52,56 include:

TABLE 2 Operating Wave Cut Off Tempera- Range Detectivity Frequency tureDetector Types¹ (λμ) D² (H_(z)) (K) Pt—S PV 0.35-0.6 30 10⁸ 295.0 Si p-nPD PV 0.4-1.0 50 10⁷ 295.0 Si p-i-n PD PV 0.4-1.1 80 10⁸ 295.0 Si APD PV0.4-0.8 80 10¹⁰ 295.0 Ge p-n PD PV 0.6-1.8 50 10⁷ 295.0 InSb p-n PD PV3.0-6.2 8 5 × 10² 77.0 PbSnTe PV 5.0-11.4 >15- 10 77.0 p-n PD 60 V/W PbSPC 0.5-3.8 15.00 300 196.0 PbSe PC 0.8-4.6 3.00 3 × 10³ 196.0 PbTe PC0.8-5.5 0.16 3 × 10³ 196.0 p-InSb PC 2.0-6.7 2.00 2 × 10⁵ 77.0 n-InSb PC1.0-3.6 30.00 2 × 10⁶ 195.0 PbSnTe PC 5.0-11.0 1.7 8 × 10⁵ 4.2 CdHgTe PC5.0-16.0 3.00 10⁴ 4.2 Ge:Au PC 2.0-9.5 0.02 10⁴ 77.0 Ge:Zn,Au PC5.0-40.0 1.00 10³ 4.2 Ge:Cu PC 5.0-30.0 3.00 10³ 4.2 Si:Al PC 2.0-16.01.00 10⁴ 27.0 Si:Sb PC 2.0-31.5 1.80 10⁴ 4.0 ATGS TC 1-1000 0.030 10295.0 (Ba,Sr)TiO₃ TC 1-1000 0.011 400 295.0 Si — 0.2-1.1 — — — Ge —0.4-1.8 — — — InAs — 1.0-3.8 — — — InGaAs — 0.8-3.0 — — — InSb — 1.0-7.0— — — InSb (77K) — 1.0-5.6 — — — HgCdTe — 1.0-25.0 — — — (77K) Note 1:PV - photo transistor type; PC: photo conductive detector type; TC:pyroelectric detector type Note 2: (10¹⁰ cmHz^(1/2) W¹)

As further shown in FIG. 1, a gain mechanism 64 is in communication withthe detectors 30,32 and the MOE 48, The gain mechanism 64 weights amagnitude of the property of an orthogonal component of a portion of thecarrier light 48 as described, for instance, by Myrick et al. in U.S.Pat. No. 6,198,531 B1 and in U.S. Pat. No. 6,529,276 B1 to Myrick.

As briefly introduced above, the beam splitter 28 is not required in analternative embodiment of the invention in which a signal from thesample W is analyzed using a PCR-type model in an off-line approach.This alternative embodiment and approach is useful, for instance,detector type; for studying signals independently. More particularly, asystem substantially as described above but without the beam splitter 28is used to take an integral of the light on a detector similar to thedetector 30 described above. By analyzing frequency-dependentintensities, results similar to those of the foregoing embodiment areproduced, although possibly with a relatively slower response time inthe present embodiment.

Also, in an additional aspect of the invention as shown in FIG. 1, asystem 68 using an electrochemical or chemometric model can be employedin conjunction with any of the foregoing embodiments to make similar orsame measurements of the light 46 reflected from the sample W, as themeasurements described in the foregoing embodiments. By way of examplebut not of limitation, the system 68 may be one as described by Myricket al. in PCT Application Number PCT/CTS2004/043742, based on U.S.Provisional Application No. 60/533,570, filed Dec. 31, 2003, which areincorporated herein by reference to these applications.

In addition to the reflectance mode described above, one or more opticalanalysis systems can operate in a transmission mode in conjunction withthe foregoing embodiments. In such a case, light is directed (passes)through the sample W, e.g., a fluid sample, and collected on anotherside of the sample W to enable study of particle density in the fluid inconjunction with the chemical content described above. For instance, thesystem 10 can be configured to operate in transmission mode where thelight is shone through the sample W to a similar detection system 110 asshown in FIG. 1 in phantom for clarity). Additionally, or alternatively,a mirrored surface 210 can be placed within the transmissive sample W toreflect the light back into the system 10.

With reference now to FIG. 3, a second exemplary embodiment of thepresent subject matter is designated generally by reference number 110.Many aspects of the optical analysis system 110 and related componentsare similar to the foregoing embodiment; thus, for the sake of brevity,only certain differences are described below. However, to provide a fulland enabling disclosure of the optical analysis system 110, when like orsimilar elements and components are not specifically described below;implicit reference is made to the foregoing descriptions.

As shown in FIG. 3, the optical analysis system 110 broadly includes ahousing 112, an illumination or light source 114, a chopper wheel 118,one or more spectral elements 120, a focusing lens 126, a beam splitter128, a first detector 130 including a multivariate optical element 148,and a second detector 132. The optical analysis system 110 furtherincludes an electrical connection 160, a pressurization sensor 162 and apurge gas assembly 164, which those skilled in the art will readilyunderstand; therefore, further description is not necessary tounderstand and practice these aspects of the invention.

With more particular reference to FIG. 3, the illumination source 114provides a light 134, which passes through a collecting Fresnel lens116A and into and through the spectral element(s) 120. In this example,the illumination source 114 is rated for at least about 10,000 hours ofoperation, which alleviates a need for redundant illumination sourcesthough they may be provided if desired. Also in this example, thecollecting Fresnel lens 116A is sized to be about 1.5 square inches andis spaced about 0.6 inches from the illumination source 114. The skilledartisan will instantly recognize that these dimensions can be adjustedaccording to particular system requirements and are not meant aslimitations of the invention.

As further shown in FIG. 3, the light 134 passes through the spectralelements 120, which filter out undesired wavelengths to define a desiredspectral region, e.g., 1500-2000 nm, in order to target a particularchemical material of interest. The light 134 is focused by focusingFresnel lens 116B, which is also sized to be about 1.5 square inches andspaced about 1 inch from the chopper wheel 118. As shown, the chopperwheel 118 reflects a portion of light 134 as a calibration or referencelight 135 and a transmitted light 144. Calibration light 135 iscollimated by lens 158 before reflecting from a first mirror 124Athrough an adjustable aperture 112B in a bulkhead 112A of the housing112. The aperture 112B is adjustable to dictate a desired amount of thecalibration light 135. Finally, calibration light 135 impinges on beamsplitter 128 thereby sending a portion 135A of calibration light 135 tothe first MOE detector 130 and a portion 135B of calibration light 135to the second or baseline detector 132. FIG. 3 further illustrates thattransmitted light 144 passes from the chopper wheel 118 into acollimating Fresnel lens 136, which in this example is sized to be about1.5 square inches and is spaced about 0.6 inches from the chopper wheel118. The transmitted light 144 passes through another adjustableaperture 112C in the bulkhead 112A and impinges upon a second mirror124B, which directs the transmitted light 144 toward a sample in acontainer C, such as mixing vat or blender. The skilled artisan willrecognize that the container could be a conveyor belt or other devicefor holding or transporting the sample and is not limited to an enclosedcontainer.

As shown in FIG. 3, the transmitted light 144 is focused by the focusingFresnel lens 126, which in this example may be round and about 15/16inches in diameter and is adjustable with an inner tube 122. Also inthis example, lens 126 may be positioned about 0.6 inches from an outersurface of the container C. As shown, the transmitted light 144, nowfocused, passes through a transmissive window 113, which in this exampleis approximately 1 inch in diameter and with an anti-reflective (AR)coating disposed on one or both sides of the lens 126. The AR coatingensures that the chemical process in the container C does not interferewith the measuring process of optical analysis system 110. Thus, thetransmitted light 144 enters the container C and reflects from thesample as a carrier light 146. The sample can be a moving mixture suchas aspirin and an excipient being blended in real time, or a pluralityof tablets passing by on a conveyor belt at high speed.

FIG. 3 further illustrates that the carrier light 146 is directed by thetube 122 in a direction of the first detector 130. Eventually, thecarrier light 146 impinges on the beam splitter 128 and a portion passesin a direction of the detector 132 for baselining with the portion 135Bof the calibration light 135. Another portion of the carrier light 146passes through MOE 148, which as noted above, has been selected for thechemical of interest based on the various components of the system 110.Finally, that portion of the carrier light 146, having passed throughthe MOE 148, is focused by lens 150 and received by the detector 152. Asdescribed above, the two signals collected by the detectors 132 and 152can be manipulated, e.g., mathematically, to extract and ascertaininformation about the sample carried by the carrier light 146.

Turning now to FIGS. 4A and 4B, detailed views of a collimating mirror226 are shown. In this example, the mirror 226 has a first end 226A anda second end 226B and is generally cylindrically shaped. The mirror 226is also coated with a reflective surface such as aluminum (Al), Au orother elements dictated by the desired spectral region. The skilledartisan will appreciate that other shapes and reflective coatings can beprovided to meet specific design requirements and characteristics of thetarget sample; thus, the mirror 226 is not limited to the exemplaryembodiment shown in FIGS. 4A and 4B.

With reference to FIGS. 3,4A and 4B, the mirror 226 is useful foranalyzing translucent, liquid samples, for example, since liquids, incontrast to powders, do not readily create a diffuse reflectance toproduce the desired carrier light 146 as shown in FIG. 3. By way ofexample operation, the lens 126 in FIG. 3 may be removed and replacedwith the mirror 226 for liquid sample analysis. Accordingly, as thelight 144 passes through the mirror 226, the light 144 is collimatedinto the liquid sample in the container C. The carrier light 146reflects from the liquid sample and returns through the first end 226A,which defines a conical shaped depression or indentation 226C. Theconical shaped indentation 226C acts to diffuse the carrier light 146 ina manner similar to the example shown in FIG. 3. Accordingly, a portionof the carrier light 146 is directed through the MOE 148 as describedabove. Again, the skilled artisan will appreciate that the invention isnot limited to this exemplary arrangement. For example, the system canbe arranged with the mirror 226 and the detectors 152, 156 on anopposing side of the container C such that the light 146 passes throughthe liquid sample into the mirror 226.

Dynamic Real-Time Detection and Measurement

The functionality of the MOC system 10 or 110 as described above allowsfor the collection of the entire spectral range of testingsimultaneously. This fact is notably different than either a systembased on either a scanning lamp or detector system or a discrete diodearray detection system. The ability to monitor over the completespectral range of interest opens up a re definition of the term“real-time” measurement and analysis.

For instance, true real-time process measurements are possible. “Realtime” refers to obtaining data without delays attendant to collectingsamples or delays due to lengthy computer processing of measurementsignals. In embodiments disclosed herein, process data can be obtainedin an instantaneous or near-instantaneous manner through using thedisclosed measurement techniques to directly monitor materials ofinterest while such materials are undergoing process steps. Long delaysdue to processing of measurement signals are avoided by opticallyprocessing the light as it is reflected from the material(s) ofinterest.

Although specific examples disclosed herein present monitoring theblending of a powdered material and examining solid tablets, the generalconcept can be extended to other phases. The present system can beutilized in analyzing solids, solutions, emulsions, gases, anddispersions, for example. In addition, while exemplary embodimentsdiscussed herein use reflectance measurements, measurements in atransmission mode would also be an appropriate method.

One of ordinary skill in the art will recognize that differingapplications may require modifications and alterations to certaincomponents in order to take full advantage of the presently-disclosedsystems. For instance, more diffusion of light has been observed insolid powders relative to liquids; accordingly, different lenses may beneeded when a liquid is monitored in order to account for suchvariations and achieve more accurate measurements.

The presently-disclosed technology can be applied to real-timemeasurements for a range of industrial applications. These include, butare not limited to monitoring of the blending of pharmaceutical powders,including excipients, additives, and active pharmaceutical materials;blending of other powders, including food and chemicals; monitoringdispersions and bi-phasic mixtures (such as insulin, emulsions); and oiland gas applications, including analyzing water content in oil, or oilcontent in water.

Inclusion of a transmissive window into a closed system allows forin-line measurement and/or non-invasive measurement of parameters suchas chemical functionality, including alcohol content of petroleumfractions or tackifier resins. Environmental applications are alsoconceivable, such as stack gas analysis, including measurement of NOx,SOX, GO, C02, or other gases in a gas stream; wastewater analysis andtreatment monitoring; and hazardous substance monitoring applicationssuch as mercury vapor detection.

Real Time Measurement of Powder Mixing

As noted above, MOC technology can be used to monitor a wide variety ofmaterials as the materials are subjected to different processes. Forinstance, the mixing of powders can be monitored. As materials areblended, the existing art does not allow for continuous, real-time,in-line measurement. Current limitations are the result of severalfactors including: moving of the powders being measured during thecourse of data acquisition and the need to connect analytical equipmentto the measurement point using fiber optic cables. This optical analysissystem is designed to allow for instantaneous measurement using ameasurement point located on the vessel.

To measure the composition of the mixture of powders during blending,the system is located in a position to shine the sampling beam into themixture. An exemplary implementation of such a measurement technique isillustrated in FIG. 6. Optic head 510 includes housing 512, requisiteMOEs and spectral elements to obtain desired information about thematerial of interest, and is generally configured and constructed inaccordance with the embodiments discussed above in conjunction withFIGS. 1-4.

In discussing various embodiments below, the term “optic head” is usedin place of the term “measurement system” in referring to the light,lenses, spectral elements, and detectors of the optical computing unitdiscussed above. As will be apparent to one skilled in the art, acomplete measurement system may utilize several instances of the opticalcomputing unit, and so the term “optic head” is used as a shorthandreference to a single instance of the optical computing unit.

Optic head 510 is connected via umbilical 514 to an appropriate powersupply and analysis computer or computers, also configured in accordancewith the principles of multivariate optical computing analysis. Aprocess point, in this illustration a mixing blender bowl 522 containingmixture 524, may thereby be monitored via optic head 510.

A port/connection 520, in one exemplary embodiment a Swagelok® brandpharmaceutical-grade stainless steel port (available from Swagelok ofSolon, Ohio), connects the opening 518 of mixing blender bowl 522therein to optic head inlet 516. Inlet 516 includes the window (13 or113 in the embodiments discussed above) through which light istransmitted and reflected for materials analysis while keeping thematerial monitored separate from the internal components of the optichead.

In one embodiment, an optic head can be configured to monitor theconcentration of a mixture of aspirin and lactose. A sapphire window islocated at the end of optic inlet 516 for interrogating the powder, andthe optic head is configured with multivariate optical elements designedto monitor aspirin concentration. A 20-watt Gilway lamp is modulatedusing 5 mm D20 and 5 mm Germanium spectral elements, and the modulatedlight is directed into the powder. The reflected light from the powderis directed through the multivariate optical elements onto a PbSdetector. A portion of the modulated light, as discussed above, ispreferably directed into a second detector. The resulting PbS detectorsignal can be compared against the second detector signal in order todetermine the concentration of aspirin.

For instance, a concentration graph such as that illustrated at 526 inFIG. 5 may be obtained, showing the rise in aspirin concentration as itis added and the leveling-off as the mixing process continues.

Embodiments in which transmitted light is measured would utilize twoports, preferably located opposite one another with the measured samplepassing between the two ports.

Real Time Measurement of Chemicals/Flowing Materials

Other embodiments of the present invention include real time measurementof flowing materials. In such embodiments, the sampling window(s) may belocated on a pipe or vessel such that interrogating illumination can beapplied to the material. For instance, a port similar to port 520 inFIG. 5 could be included on a pipe to allow for sampling of the materialinside the pipe. The window may be positioned directly on the pipe, oron a small diversion away from the main flow path, as appropriate underthe circumstances. Such embodiments could also include sampling of vaporsystems within a stack to monitor combustion gases or flowing processstream such as water containing other materials.

Real Time Measurement of Moving Containers

Still further embodiments of the present invention include the real timemeasurement of materials in containers, such as vials or bins where thecontainer is either at least partially open to the outside environmentor transmissive to the sampling illumination. Such containers could bestationary or in motion. A container could also include a conveyor ortrough carrying material. Typical applications could include themonitoring the progress of a chemical reaction or the content of samplesmoving past a measurement location.

For instance, FIG. 6 illustrates a plurality of samples 552 positionedon a rotating disc conveyor 550. One of ordinary skill in the art willrecognize that the samples may be positioned on a conveyor belt or movedusing another automated conveyance, depending upon the particulartesting circumstances and environment. The samples 552 are illustratedas tablets in FIG. 6, which could include capsules, caplets, pills, andother individualized units of pharmaceutical (or other) product.

As shown in FIG. 6, tablets 552 are rotated into the view of opticalinlet 516′ for optic head 51OY, which as discussed earlier, includeshousing 512′ and umbilical 514′, as well as requisite internalcomponents, filters, and MOEs to perform the desired testing operations.Embodiments of the present invention may be configured to monitor around5 tablets per second, with the tablets in continuous motion.

As discussed in conjunction with the optic head of FIG. 5, in oneembodiment, a PbS detector can be used in conjunction with a sapphirewindow and D20 and germanium spectral elements to monitor theconcentration of aspirin and lactose. Unlike the system in FIG. 5, thesapphire window of the optic inlet 516 is positioned above the samplessuch that the beam of light is focused downward onto the samples on theconveyor belt. However, the optical principles remain the same. Graph528 represents exemplary results that would be obtained by samples ofvarying concentration of aspirin, with each spike representing when asample is in full view of the optic head 510′.

Samples 552 may comprise the actual samples to be measured, such as thetablet end-product illustrated in FIG. 6 and discussed below inconjunction with FIG. 7. However, one of ordinary skill in the art willrecognize that samples 552 may also comprise transparent containers andthe like, which may contain a dispersion or suspension of a solidmaterial in a liquid or a solution, or solid materials. For instance,trays of powder can be placed on an automated conveyance and broughtinto view of optic head 510′ in a similar manner.

Instead of moving samples 552, one of ordinary skill in the art willnote that measurement device 510′ could be repositioned to examine thesamples 552 by appropriate machinery such as overhead tracks, roboticarms, and the like. The skilled artisan will recognize that in suchcases, appropriate care would preferably be taken to ensure that forcelevels applied to the measurement device and its internal componentsremained within tolerable levels.

Integrated Real-Time Process Management Us in MOC Systems

An illustration of one embodiment of real-time process management isfound in FIG. 7. A plurality of optic heads 710 are shown integratedinto various process steps 720,730, and 740. Process steps 720,730, and740 can represent stages or steps of any number of industrial operationsin which materials are handled or manipulated, and in which physicalstate or compositional data is desirable. In accordance with the systemembodiments discussed above, each optic head 710 a, by c, d, e isprovided with MOEs and other optical components specifically tailored tothe materials characteristics which are to be monitored at each step,and interfaced with the process control computer(s). The analysis dataultimately provided by collection points 710 is shown at 722,724,732,742, and 744. Such data can be obtained using single or multiple processcontrol computers configured to collect, analyze, and otherwise handlethe data from the detectors within the optic heads in accordance withthe principles of multivariate optical computing discussed above.

Assume, for example, that process steps 720, 730, and 740 representvarious stages in a pharmaceutical manufacturer's production line forblending powder and forming tablets. The skilled artisan will recognizethat pharmaceutical manufacturing often entails strict control andmonitoring of material composition and mixing at every stage ofproduction.

The initial steps of obtaining and readying component materials in apharmaceutical process could be represented at 720. Optic head 710 acould be used to monitor the incoming raw materials in trays or onconveyors and provide inspection and quantification data 712, such aspurity data. Optic head 710 b could be configured to the monitorincoming material(s) as they undergo an initial process stage, forexample, providing chemical drying characteristics 724 as the rawmaterials are dried.

Process step 730 could represent mixing of active and excipientcomponents into a powder, and optic head 710 c could provide data 732 onmixing progress. For instance, optic head 710 c could be interfaced withthe mixing container and provide data tracking active ingredientconcentration over time as shown in FIG. 5. Based on such concentration,requisite steps could be taken to ensure the optimal amount of activecomponent is in the resulting mix or otherwise adjust the mixing processby altering temperature or the like.

Step 740 could represent pressing tablets, with optic heads 710 d and710 e positioned above a conveyor moving the completed tablets, andproviding data 742 on tablet components and homogeneity, and data oncoating thickness and uniformity 744.

Step 750 represents the final portions of the manufacturing processwhich are not monitored, such as packaging. One skilled in the art will,of course, recognize that step 750 could represent the entry into adifferent process which is itself monitored by one or more opticalanalysis systems.

The invention may be better understood from the following tests andexamples.

Example I System I

A first breadboard system was constructed and used to test a mixture ofpowders.

System I Components:

Illumination: 20 W Gilway lamp

Spectral elements: 5 mm deuterium oxide (D20), 5 mm Germanium

Optical window: fiber optic probe

Detector: InAr detector from Judson

MOE: specific to test

Procedure and Results of Static Testing Using System I

A powdered sample with a known composition was placed in a dish and thefiber optic probe was placed in contact with the powder. The output ofthe detectors was monitored and recorded.

Example II System II

A system similar to the optical analysis system 10 shown in the figureswas constructed and used to make static measurements on aspirin/lactose.

System II Components:

Illumination: 20 W Gilway lamp

Spectral elements: 5 mm D20, 5 mm Germanium

Optical window: none

Detector: PbS detector from New England Photoconductor

MOE: specific to test conditions.

Procedure and Results of Static Testing Using System II

A powdered sample with a known composition was placed in a dish and thesystem light beam was focused on the powder. The output of the detectorswas monitored and recorded. Aspirin/lactose samples covering the rangeof 100% aspirin to 100% lactose were tested.

Example III System III

A system similar to the optical analysis system 10 shown in the figureswas constructed and used to make dynamic measurements onaspirin/lactose.

System III Components:

Illumination: 20 W Gilway lamp

Spectral elements: 5 mm D20, 5 mm Germanium

Optical window: sapphire window

Detector: PbS detector from New England Photoconductor

MOE: specific to test conditions.

Procedure and Results of Dynamic Testing Using System III

The Aspirin/Lactose testing was made on a mixer bowl containing lactoseand the system measured as aspirin was added to the system and mixed.Specifically, lactose powder was placed in the bowl of a mixer and themeasurement system was attached the bowl using a Swagelok® brandfitting. A sapphire window was used to contain the powder in the bowland allow the system to interrogate the powder. With the mixer turning,known amounts of aspirin were added and the system output signal wasmonitored and recorded. Aspirin was added in several allotments to about37% final aspirin concentration.

Example IV System IV

A system similar to the optical analysis system 10 shown in the figureswas constructed and used to make static measurements on aspirin/lactose.

System IV Components:

Illumination: 5 W Gilway lamp

Spectral elements: 5 mm D20, 5 mm Germanium

Optical window: none

Detector: PbS detector from New England Photoconductor

MOE: specific to test conditions.

Procedure and Results of Dynamic Testing Using System III

Similar to the examples above.

Although the invention has been described in such a way as to provide anenabling disclosure for one skilled in the art to make and use theinvention, it should be understood that the descriptive examples of theinvention are not intended to limit the present invention to use only asshown in the figures. For instance, the housing 16 can be shaped as asquare, an oval, or in a variety of other shapes. Further, a variety oflight sources can be substituted for those described above. It isintended to claim all such changes and modifications as fall within thescope of the appended claims and their equivalents. Thus, whileexemplary embodiments of the invention have been shown and described,those skilled in the art will recognize that changes and modificationsmay be made to the foregoing examples without departing from the scopeand spirit of the invention.

That which is claimed is:
 1. A system for real-time processing andmonitoring, comprising: a light source to provide an illumination lightand a calibration light; an optical element to separate the illuminationlight and the calibration light; an optical element to direct theillumination light to a sample; an optical element to direct thecalibration light to a first detector and a second detector; an opticalelement to collect light backscattered from the sample; an opticalelement to separate light backscattered from the sample into a firstscattered light portion and a second scattered light portion; an opticalelement to direct the first scattered light portion through at least onemultivariate optical element to the first detector; and an opticalelement to direct the second scattered light portion to the seconddetector.
 2. The system of claim 1 wherein the optical element to directthe calibration light to a first detector and a second detectorcomprises an optical element to separate the calibration light into afirst calibration light portion directed to the first detector and asecond calibration light portion directed to the second detector.
 3. Thesystem of claim 1 wherein the first calibration light portion passesthrough the at least one multivariate optical detector.
 4. The system ofclaim 1 wherein the optical element to direct the calibration light to afirst detector and a second detector comprises an adjustable aperture toregulate an amount of calibration light directed to the first detectorand the second detector.
 5. The system of claim 1 wherein the opticalelement to direct the illumination light to a sample comprises anadjustable aperture to regulate an amount of illumination light to thesample and a reflective element to separate the illumination light andlight backscattered from the sample.
 6. The system of claim 1 where theoptical element to direct the calibration light to the first and asecond detector is a chopper wheel.
 7. The system of claim 1 wherein theoptical element to direct the calibration light to the first and seconddetectors is an optical modulator operating at a frequency selectedaccording to a speed of the sample across a sample area in the system.8. A method for real-time processing and monitoring, comprising:separating a source light into an illumination light and a calibrationlight; illuminating a sample with the illumination light; dividing lightcarrying information about the sample with a beam splitter into a firstlight portion and a second light portion; directing the first lightportion through at least one multivariate optical element to produce afirst signal; detecting the first signal at a first detector; directingthe second light portion in a direction of a second detector, the seconddetector configured to detect the second light portion; detecting aportion of the calibration light at the first detector; and determiningat least one selected property of the sample based upon a first detectoroutput and a second detector output.
 9. The method as in claim 8 whereinthe sample is a powder.
 10. The method as in claim 9 further comprisingmixing a first component and a second component in the powder.
 11. Themethod as in claim 10 wherein determining the at least one selectedproperty of the sample comprises measuring the amount of the firstcomponent in the powder.
 12. The method as in claim 8, wherein thesample is an opaque fluid.
 13. The method as in claim 8, whereindetermining at least one selected property of the sample is completed inless than 1/100 of a second.
 14. The method as in claim 8, whereindetermining at least one selected property of the sample is completed inless than 1/10 of a second.
 15. The method as in claim 8, whereindetermining at least one selected property of the sample is completed inless than 1 second.
 16. The method as in claim 8, wherein determining atleast one selected property of the sample is completed in less than 5seconds.
 17. The method as in claim 8, wherein determining at least oneselected property of the sample is completed in less than 30 seconds.18. The method as in claim 8 wherein separating a source light into anillumination light and a calibration light comprises modulating thesource light at a frequency selected according to a speed of the sampleacross a sampling area.
 19. A method for real-time processing andmonitoring, comprising: positioning a sample proximal to an optic windowin an optical sensor; separating a source light into a spectral-specificlight and a calibration light; illuminating a sample with thespectral-specific light through an optic window, the optic windowconfigured to focus the spectral-specific light into the sample;dividing light carrying information about the sample with a beamsplitter into a first light portion and a second light portion, thefirst light portion and the second light portion having substantiallysimilar spectral characteristics; directing the first light portionthrough at least one multivariate optical element to produce a firstsignal; detecting the first signal at a first detector; detecting aportion of the calibration light at the first detector; directing thesecond light portion in a direction of a second detector, the seconddetector configured to detect the second light portion; and determiningat least one selected property of the sample based upon a first detectoroutput and a second detector output.
 20. The method of claim 19 whereinthe sample is a powder; and further comprising blending the powder bymixing a first component and a second component.
 21. The method as inclaim 20, wherein the selected property of the sample is an amount ofthe first component of the powder.
 22. The method as in claim 20,wherein the selected property of the sample is a particulate size of thefirst component of the powder.
 23. The method as in claim 20, whereinthe selected property of the sample is a secondary property of thesecond component of the sample.
 24. The method as in claim 20, furthercomprising assessing an homogeneity asymptote of the powder.
 25. Themethod as in claim 19 wherein the sample comprises a suspension of asolid material in a liquid.
 26. The method as in claim 19 whereinpositioning a sample proximal to an optic window in an optical sensorcomprises placing trays of powder on a conveyance.
 27. The method as inclaim 19 wherein positioning a sample proximal to an optic window in anoptical sensor comprises positioning a plurality of sample portionsproximal to a plurality of optical heads, each optical head having adedicated multivariate optical element; and directing the first lightportion through at least one multivariate optical element comprisesdirecting the first light portion through the dedicated multivariateoptical element for each optical head.
 28. The method as in claim 19further wherein: positioning a sample proximal to an optic window in anoptical sensor comprises moving the sample on a conveyor belt at a speedacross a sampling area in the optical sensor; and separating a sourcelight into a spectral-specific light and a calibration light includesmodulating the source light at a frequency selected according to thespeed of the sample across the sampling area in the optical detector.